Hemicholinium lipids and use thereof

Abstract

Compounds of the present invention are those having the formula: <IMAGE> I where R is a linear or branched chain of 1 to 22 carbon atoms selected from the group consisting of alkyl, alkenyl or alkynyl or said C1 to C22 chains substituted with -SR3, -OR3, -NHR3, -CH3, or -C(O)OR2 where R2 is hydrogen or C1 to C6 alkyl; R1 is hydrogen, C1 to C6 alkyl, -SR3, -OR3, -NHR3, -NR'3R3, or -C(O)OR2 where R2 is as previously defined; R3 and R'3 are the same or different and are hydrogen, C1 to C6 alkyl, alkylthioalkyl, alkoxyalkyl, aminoalkyl, aminoalkyl substituted with phenyl, substituted phenyl, benzoyl, substituted benzoyl, heteroaryl or substituted heteroaryl; R4 is hydrogen, C1 to C6 alkyl, or -C(O)OR2 where R2 is defined previously; R5 is hydrogen, C1 to C6 alkyl, phenyl, or substituted phenyl; R6 is hydrogen, C1 to C6 alkyl, phenyl, substituted phenyl, heterroaryl or substituted heteroaryl; m is an integer from 0 to 3; and n is an integer from 1 to 23. The compounds provide useful methods of inhibiting carnitine palmitoyltransferase.

We claim: 
     
       1. An optically active or racemic mixture of a compound of the formula: ##STR12## where R is a linear or branched chain of 10 to 22 carbon atoms selected from the group consisting of alkyl, alkenyl or alkynyl or said C 10  to C 22  chains substituted with --SR 3 , --OR 3 , --NHR 3 , --CH 3 , or --C(O)OR 2  where R 2  is hydrogen or C 1  to C 6  alkyl; R 1  is --SR 3  or --OR 3  ;   R 3  is hydrogen, C 1  to C 6  alkyl, alkylthioalkyl, alkoxyalkyl, aminoalkyl, aminoalkyl substituted with phenyl, substituted phenyl, benzoyl, substituted benzoyl, heteroaryl or substituted heteroaryl;   R 4  is hydrogen, C 1  to C 6  alkyl, or --C(O)OR 2  where R 2  is defined previously;   R 5  is hydrogen, C 1  to C 6  alkyl, phenyl, or substituted phenyl;   R 6  is hydrogen, C 1  to C 6  alkyl, phenyl, substituted phenyl, heteroaryl or substituted heteroaryl;   m is 1;   and n is an integer from 1 to 23.   
     
     
       2. The compound of claim 1 wherein R 4  is hydrogen. 
     
     
       3. The compound of claim 1 wherein R is C 10  to C 20  alkyl substituted with CH 3 . 
     
     
       4. The compound of claim 2 wherein n is an integer of from 1 to 14. 
     
     
       5. The compound of claim 3 wherein R 1  is --OR 3  is hydrogen or C 1  to C 6  alkyl. 
     
     
       6. The compound of claim 5 wherein R 3  is hydrogen or methyl. 
     
     
       7. The compound of claim 3 wherein R 6  is hydrogen, C 1  to C 6  alkyl or phenyl. 
     
     
       8. The compound of claim 7 wherein R 6  is hydrogen. 
     
     
       9. The compound of claim 7 wherein R 5  is hydrogen or C 1  to C 6  alkyl. 
     
     
       10. The compound of claim 9 wherein R 5  is C 1  to C 3  alkyl. 
     
     
       11. The compound of claim 10 wherein X is a pharmaceutically acceptable inorganic acid addition salt. 
     
     
       12. A method for inhibiting the enzyme carnitine palmitoyltransferase in mammals comprising treating said mammals with an effective amount of a compound according to claim 1.